Biomarker Analyses from Pivotal Phase 3 CLEAR Trial in Patients with Advanced Renal Cell Carcinoma Will Be Featured in an Oral Presentation

晚期肾细胞癌患者关键性3期CLEAR试验的生物标志物分析将在口头报告中进行

Additional Data From Eisai's Pipeline Provide Insights Into Metastatic Breast Cancer and Other Solid Tumors

卫材管道的其他数据提供了对转移性乳腺癌和其他实体瘤的见解

NUTLEY, N.J., May 23, 2024 /PRNewswire/ -- Eisai announced today the presentation of research across multiple types of cancer from its oncology portfolio and pipeline during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (#ASCO24), which is taking place virtually and in-person in Chicago, Illinois from May 31 to June 4..

新泽西州纳特利（NUTLEY，N.J.），2024年5月23日/PRNewswire/--卫材（Eisai）今天宣布，在2024年美国临床肿瘤学会（ASCO）年会（ASCO24）期间，从其肿瘤学组合和管道中介绍了多种类型癌症的研究，该年会将于5月31日至6月4日在伊利诺伊州芝加哥市举行。。

Notable data include an oral presentation on biomarker analyses from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial (NCT02811861), which evaluated lenvatinib (LENVIMA®), the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai, plus pembrolizumab (KEYTRUDA®), Merck's anti-PD-1 therapy, versus sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (Abstract #4504).

值得注意的数据包括来自关键的3期CLEAR（研究307）/KEYNOTE-581试验（NCT02811861）的生物标志物分析的口头报告，该试验评估了由卫材发现的口服多受体酪氨酸激酶抑制剂lenvatinib（LENVIMA®），加上pembrolizumab（KEYTRUDA®），默克公司的抗PD-1疗法，与舒尼替尼用于晚期肾细胞癌患者的一线治疗（摘要#4504）。

An analysis of patterns of disease progression and subsequent therapy from this trial will also be presented in a poster presentation (Abstract #4524)..

该试验对疾病进展模式和后续治疗的分析也将在海报展示中呈现（摘要#4524）。。

'At Eisai, we let the science drive us to new approaches that accelerate progress in oncology, while also remaining grounded in our human health care concept that reinforces our commitment to prioritize the needs of patients and families impacted by a cancer diagnosis,' said Dr. Takashi Owa, Chief Scientific Officer, Senior Vice President, Eisai Co., Ltd.

卫材株式会社首席科学官、高级副总裁大坂隆史博士说：“在卫材，我们让科学推动我们采用新的方法来加速肿瘤学的进步，同时也以我们的人类医疗保健概念为基础，这加强了我们对优先考虑受癌症诊断影响的患者和家庭需求的承诺。”。

'With this in mind, we look forward to sharing research that provides further insight into the role of lenvatinib plus pembrolizumab as a first-line standard of care option in advanced renal cell carcinoma, as well as research that explores various modalities in our pipeline for the potential treatment of advanced diseases with the goal of improving patients' lives.'.

“考虑到这一点，我们期待着分享研究，进一步了解lenvatinib加pembrolizumab作为晚期肾细胞癌一线护理选择的作用，以及探索我们管道中各种模式的研究，以改善患者生活为目标的晚期疾病的潜在治疗方法。”。

Other key research of note from Eisai's pipeline include an oral presentation of Phase 3 data from the JBCRG-M06/EMERALD study in Japan evaluating trastuzumab and pertuzumab in combination with Eisai's eribulin mesylate or a taxane in patients with HER2-positive, locally advanced or metastatic breast cancer (NCT03264547; Abstract #1007).

卫材管道中值得注意的其他关键研究包括日本JBCRG-M06/EMERALD研究的第三阶段数据的口头介绍，该研究评估了曲妥珠单抗和帕妥珠单抗联合卫材的甲磺酸依利布林或紫杉烷治疗HER2阳性，局部晚期或转移性乳腺癌（NCT03264547；摘要#1007）。

Additional pipeline research to be presented in poster sessions include an overview of a Phase 2 study of BB-1701, an antibody drug conjugate targeting HER2, in previously treated patients with HER2-positive or HER2-low unresectable or metastatic breast cancer (NCT06188559; Abstract #TPS1122), findings from a Phase 1b trial of tasurgratinib (development code: E7090) with or without endocrine therapies for patients with ER positive, HER2 negative recurrent/metastatic breast cancer after receiving a CDK4/6 inhibitor (NCT04572295; Abstract #3103), as well as the dose-expansion part of a Phase 1b global study of E7386 (a Wnt/β-catenin pathway modulator) in combination with lenvatinib in patients with hepatocellular carcinoma and other solid tumors including endometrial cancer (NCT04008797; Abstract #TPS3169)..

将在海报会议上介绍的其他管道研究包括对先前接受过HER2阳性或HER2低不可切除或转移性乳腺癌治疗的患者（NCT06188559；摘要#TPS1122）的BB-1701（一种靶向HER2的抗体-药物偶联物）的2期研究的概述，对接受CDK4/6抑制剂（NCT04572295；摘要#3103）后ER阳性，HER2阴性复发/转移性乳腺癌患者进行内分泌治疗的tasurgratinib 1b期试验（开发代码：E7090）的发现，以及1b期全球研究的剂量扩展部分E7386（Wnt/β-连环蛋白途径调节剂）联合lenvatinib治疗肝细胞癌和其他实体瘤（包括子宫内膜癌）患者（NCT04008797；摘要#TPS3169）。。

This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval..

本版本讨论了FDA批准产品的研究化合物和研究用途。它并不是为了传达关于疗效和安全性的结论。不能保证任何研究化合物或FDA批准产品的研究用途将成功完成临床开发或获得FDA批准。。

The full list of Eisai presentations is included below. These abstracts will be made available via the ASCO website on Thursday, May 23, 2024, at 5:00 PM EDT.

卫材演讲的完整列表如下。这些摘要将于2024年5月23日星期四美国东部夏令时下午5:00通过ASCO网站提供。

Cancer Type

癌症类型

Study/Compound

研究/化合物

Abstract Title

摘要标题

Abstract Type & Details

抽象类型和详细信息

Lenvatinib Plus Pembrolizumab

乐伐替尼加Pembrolizumab

Genitourinary Cancer

泌尿生殖系统癌

CLEAR

清除

Biomarker analyses in patients with advanced renal cell carcinoma (aRCC) fromthe phase 3 CLEAR trial

来自3期CLEAR试验的晚期肾细胞癌（aRCC）患者的生物标志物分析

Oral Abstract Session Abstract #4504 June 3, 2024 10:00 AM EDT / 9:00 AM CDT

口头摘要会议摘要#4504 2024年6月3日美国东部夏令时上午10:00/美国东部夏令时上午9:00

Genitourinary Cancer

泌尿生殖系统癌

CLEAR

清除

Lenvatinib plus pembrolizumab (L+P) vssunitinib (S) in advanced renal cell carcinoma (aRCC): Patterns of progression and subsequent therapy in the CLEAR trial

Lenvatinib联合pembrolizumab（L+P）vssunitinib（S）治疗晚期肾细胞癌（aRCC）：CLEAR试验中的进展模式和后续治疗

Poster Session Abstract #4524 June 2, 2024 10:00 AM EDT / 9:00 AM PM CDT

海报会议摘要#2024年6月2日上午10:00 EDT/晚上9:00 CDT

Melanoma

黑色素瘤

LEAP-004

LEAP-004

Lenvatinib (len) plus pembrolizumab(pembro) in patients with advanced melanoma that progressed on anti-PD-(L)1 therapy: Over 4 years of follow-up from thephase 2 LEAP-004 study

Lenvatinib（len）联合pembrolizumab（pembro）治疗晚期黑色素瘤患者，这些患者在抗PD-（L）1治疗中取得了进展：2期LEAP-004研究的随访超过4年

Poster Session Abstract #9559 June 1, 2024 2:30 PM EDT / 1:30 PM CDT

海报会议摘要35592024年6月1日下午2:30 EDT/下午1:30 CDT

Lenvatinib

乐伐替尼

Differentiated Thyroid Cancer

分化型甲状腺癌

Real-World Evidence

真实世界的证据

Patients with radioiodine-refractory differentiated thyroid cancer (RAI-R DTC) with BRAF V600E and/or K601E mutationstatus: A real-world view of effectiveness oflenvatinib monotherapy

具有BRAF V600E和/或K601E突变状态的放射性碘难治性分化型甲状腺癌（RAI-R DTC）患者：envatinib单药治疗有效性的现实观点

Poster Session Abstract #6098 June 2, 2024 10:00 AM EDT / 9:00 AM CDT

海报会议摘要#6098 2024年6月2日美国东部夏令时上午10:00/东部夏令时上午9:00

Gastrointestinal Cancer

胃肠道癌

REFLECT

反映

ctDNA analysis of patients (pts) withunresectable hepatocellular carcinoma (uHCC) treated with lenvatinib (LEN) or sorafenib (SOR) as 1L therapy

lenvatinib（LEN）或索拉非尼（SOR）作为1L治疗的不可切除肝细胞癌（uHCC）患者的ctDNA分析

Poster Session Abstract #4094 June 1, 2024 2:30 PM EDT / 1:30 PM CDT

海报会议摘要#4094 2024年6月1日下午2:30 EDT/下午1:30 CDT

Eribulin

埃里布林

Breast Cancer

乳腺癌

JBCRG-M06/ EMERALD

JBCRG-M06/祖母绿

Trastuzumab and pertuzumab incombination with eribulin mesylate or a taxane as first-line chemotherapeutictreatment for HER2-positive, locally advanced or metastatic breast cancer: Results of a multicenter, randomized, non-inferiority phase 3 trial in Japan (JBCRG-M06/EMERALD)

曲妥珠单抗和帕妥珠单抗联合甲磺酸埃里布林或紫杉烷作为HER2阳性，局部晚期或转移性乳腺癌的一线化疗药物：日本多中心，随机，非劣效性3期试验（JBCRG-M06/EMERALD）的结果

Oral Abstract Session Abstract #1007 June 1, 2023 6:00 PM EDT / 5:00 PM CDT

口头摘要会议摘要#1007 2023年6月1日下午6:00 EDT/下午5:00 CDT

Pipeline

管道

Breast Cancer

乳腺癌

BB-1701

BB-1701

An open-label, multicenter, phase 2 study toevaluate the safety and efficacy of BB-1701,a novel antibody drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2), in previously treated patients with HER2-positive (HER2+) or HER2-low unresectableor metastatic breast cancer (BC) .

一项开放标签，多中心，2期研究评估BB-1701（一种靶向人表皮生长因子受体2（HER2）的新型抗体-药物偶联物（ADC））在先前治疗的HER2阳性（HER2+）或HER2低不可切除或转移性乳腺癌（BC）患者中的安全性和有效性。

Poster Session Abstract #TPS1122 June 2, 2024 10:00 AM EDT / 9:00 AM CDT

海报会议摘要#TPS1122 2024年6月2日美国东部夏令时上午10:00/美国东部夏令时上午9:00

tasurgratinib

塔苏拉替尼

Phase Ib trial of tasurgratinib (E7090) withor without endocrine therapies for patients(pts) with ER+, HER2− recurrent/metastaticbreast cancer (BC) after receiving a CDK4/6inhibitor

接受CDK4/6抑制剂治疗ER+，HER2-复发/转移性乳腺癌（BC）的患者（pts）接受或不接受内分泌治疗的tasurgratinib（E7090）的Ib期试验

Poster Session Abstract #3103 June 1, 2024 10:00 AM EDT / 9:00 AM CDT

海报会议摘要#3103 2024年6月1日美国东部夏令时上午10:00/东部夏令时上午9:00

H3B-6545

H3B-6545

H3B-6545 in women with locally advanced/metastatic estrogen receptor-positive (ER+), HER2 negative (-) breastcancer (BC)

H3B-6545在局部晚期/转移性雌激素受体阳性（ER+），HER2阴性（-）乳腺癌（BC）女性中的表达

Rapid Oral Session Abstract #1015 June 3, 2024 12:36 PM EDT / 11:36 AM CDT

快速口头会议摘要#1015 2024年6月3日美国东部夏令时下午12:36/美国东部夏令时上午11:36

H3B-6545

H3B-6545

H3B-6545 + palbociclib in patients (pts) withlocally advanced/metastatic estrogenreceptor-positive (ER+), HER2 negative (-)breast cancer (BC)

H3B-6545+palbociclib治疗局部晚期/转移性雌激素受体阳性（ER+），HER2阴性（-）乳腺癌（BC）患者

Poster Session Abstract #1051 June 2, 2024 10:00 AM EDT / 9:00 AM CDT

海报会议摘要#1051 2024年6月2日美国东部夏令时上午10:00/东部夏令时上午9:00

Solid Tumors

实体瘤

E7386

E7386型

Dose-expansion part of a phase 1b global study of E7386 in combination withlenvatinib (LEN) in patients (pts) withhepatocellular carcinoma (HCC) and other solid tumors including endometrial cancer(EC)

E7386联合Lenvatinib（LEN）治疗肝细胞癌（HCC）和其他实体瘤（包括子宫内膜癌（EC））患者的1b期全球研究的剂量扩展部分

Poster Session Abstract #TPS3169 June 1, 2024 10:00 AM EDT / 9:00 AM CDT

海报会议摘要#TPS3169 2024年6月1日美国东部夏令时上午10:00/美国东部夏令时上午9:00

In March 2018, Eisai and Merck (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with Merck's anti-PD-1 therapy, pembrolizumab. Eisai and Merck are studying the lenvatinib plus pembrolizumab combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types across multiple clinical trials..

2018年3月，卫材和默克（在美国和加拿大以外称为MSD）通过一家附属公司，就lenvatinib的全球共同开发和共同商业化进行了战略合作，既可以作为单一疗法，也可以与默克的抗PD-1疗法pembrolizumab联合使用。Eisai和Merck正在通过LEAP（lenvatinib和pembrolizumab）临床计划在多种临床试验中研究lenvatinib加pembrolizumab联合治疗各种肿瘤类型。。

In May 2023, Eisai entered into a joint development agreement with Bliss Biopharmaceutical (Hangzhou) Co., Ltd. (Headquarters: Zhejiang Province, China, 'BlissBio'), for BB-1701, a HER2-targeting antibody drug conjugate (ADC), with option rights for a strategic collaboration. Eisai and BlissBio are currently investigating BB-1701 in a Phase 2 clinical trial in Japan and the United States for breast cancer, and a Phase 1/2 clinical trial in the United States and China for HER2-expressing solid tumors. .

2023年5月，卫材与Bliss Biopharmaceutical（杭州）有限公司（总部：中国浙江省，“BlissBio”）就BB-1701（一种靶向HER2的抗体-药物偶联物（ADC））签订了联合开发协议，并拥有战略合作的选择权。Eisai和BlissBio目前正在日本和美国进行乳腺癌的2期临床试验，以及在美国和中国进行的表达HER2的实体瘤的1/2期临床试验中研究BB-1701。。

About BB-1701BB-1701 is an antibody drug conjugate (ADC) that is composed of Eisai's in-house developed cytotoxic agent eribulin, and an anti-HER2 antibody using a linker, and is expected to have anti-tumor effects on breast, lung and other solid tumors that express HER2 through direct cytotoxicity (including immunogenic cell death), a bystander effect* and immune response-induced cell death..

关于BB-1701BB-1701是一种抗体-药物偶联物（ADC），由卫材内部开发的细胞毒性剂eribulin和使用接头的抗HER2抗体组成，预计对乳腺癌，肺癌和其他通过直接细胞毒性（包括免疫原性细胞死亡），旁观者效应*和免疫应答诱导的细胞死亡表达HER2的实体瘤具有抗肿瘤作用。。

*Bystander effect: When the cytotoxic agent and antibody parts of an ADC are separated inside a targeted antigen-positive cancer cell, the released cytotoxic agent also affects neighboring antigen-negative cancer cells and the component cells of the cancer microenvironment.

*旁观者效应：当ADC的细胞毒性剂和抗体部分在靶向抗原阳性癌细胞内分离时，释放的细胞毒性剂也影响邻近的抗原阴性癌细胞和癌症微环境的组成细胞。

About E7386E7386 is a selective inhibitor of the interaction between the cAMP response element-binding protein (CREB) binding protein (CBP) / β-catenin and a modulator of the Wnt / β-catenin signaling pathway. E7386 is thought to block the protein-protein interaction between a transcriptional co-activator, CBP and β-catenin, resulting in the inhibition of Wnt / β-catenin pathway-dependent gene expression.

关于E7386E7386是cAMP反应元件结合蛋白（CREB）结合蛋白（CBP）/β-连环蛋白与Wnt/β-连环蛋白信号通路调节剂之间相互作用的选择性抑制剂。E7386被认为可以阻断转录共激活因子CBP和β-连环蛋白之间的蛋白质-蛋白质相互作用，从而抑制Wnt/β-连环蛋白途径依赖性基因表达。

Since E7386 is thought to act on the CBP / β-catenin transcription complex located at the most downstream of the Wnt signaling, it is expected to inhibit not only ligand-dependent activation but also activation caused by gene mutations in Wnt signaling factors such as adenomatous polyposis coli (APC) and β-catenin.

由于E7386被认为作用于位于Wnt信号传导最下游的CBP/β-连环蛋白转录复合物，因此预计它不仅可以抑制配体依赖性激活，还可以抑制Wnt信号传导因子如腺瘤性息肉病（APC）和β-连环蛋白基因突变引起的激活。

E7386 is created through collaboration research between Eisai and PRISM BioLab Co., Ltd. (Headquarters: Kanagawa).

E7386是通过卫材和PRISM BioLab Co.，Ltd.（总部：神奈川）的合作研究创建的。

About HALAVEN® (eribulin mesylate) Injection (0.5 mg/mL)HALAVEN (eribulin mesylate) Injection is indicated for the treatment of patients with metastatic breast cancer (mBC) who have previously received at least 2 chemotherapeutic regimens for the treatment of metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting.

关于HALAVEN®（甲磺酸依瑞布林）注射液（0.5 mg/mL）HALAVEN（甲磺酸依瑞布林）注射液适用于治疗转移性乳腺癌（mBC）患者，这些患者先前已接受至少2种化疗方案治疗转移性疾病。先前的治疗应该包括蒽环类药物和紫杉烷在辅助或转移环境中。

HALAVEN is also indicated for the treatment of patients with unresectable or metastatic liposarcoma who have received a prior anthracycline-containing regimen..

HALAVEN也适用于治疗先前接受过含蒽环类药物治疗的不可切除或转移性脂肪肉瘤患者。。

Eribulin is a microtubule dynamics inhibitor in the halichondrin class with a novel mechanism of action, developed in-house by Eisai. Structurally, eribulin is a simplified and synthetically produced version of halichondrin B, a natural product isolated from the marine sponge Halichondria okadai. Eribulin is believed to work by inhibiting the growth phase of microtubule dynamics which prevents cell division.

Eribulin是halichondrin类的微管动力学抑制剂，具有由Eisai内部开发的新型作用机制。在结构上，eribulin是halichondrin B的简化和合成版本，halichondrin B是从海绵Halichondria okadai中分离出来的天然产物。Eribulin被认为通过抑制微管动力学的生长阶段来阻止细胞分裂。

In addition, non-clinical studies showed eribulin's unique actions in the tumor microenvironment such as an increase in vascular perfusion and permeability in tumor cores, promotion of the epithelial state, decrease in capacity of breast cancer cells to migrate, etc..

此外，非临床研究表明，埃里布林在肿瘤微环境中具有独特的作用，例如增加肿瘤核心的血管灌注和通透性，促进上皮状态，降低乳腺癌细胞的迁移能力等。。

Important Safety Information for HALAVEN

HALAVEN的重要安全信息

Warnings and Precautions

警告和注意事项

Neutropenia: Severe neutropenia (ANC <500/mm3) lasting >1 week occurred in 12% of patients with mBC. Febrile neutropenia occurred in 5% of patients with mBC and 2 patients (0.4%) died from complications. Patients with mBC with elevated liver enzymes >3 × ULN and bilirubin >1.5 × ULN experienced a higher incidence of Grade 4 neutropenia and febrile neutropenia than patients with normal levels.

中性粒细胞减少症：12%的mBC患者发生持续>1周的严重中性粒细胞减少症（ANC<500/mm3）。5%的mBC患者发生发热性中性粒细胞减少症，2例（0.4%）死于并发症。肝酶升高>3×ULN且胆红素>1.5×ULN的mBC患者比正常水平的患者发生4级中性粒细胞减少症和发热性中性粒细胞减少症的发生率更高。

Monitor complete blood cell counts prior to each dose, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. Delay administration and reduce subsequent doses in patients who experience febrile neutropenia or Grade 4 neutropenia lasting >7 days..

在每次给药前监测全血细胞计数，并增加发生3级或4级血细胞减少症的患者的监测频率。对于持续7天以上的发热性中性粒细胞减少症或4级中性粒细胞减少症患者，延迟给药并减少后续剂量。。

Peripheral Neuropathy: Grade 3 peripheral neuropathy occurred in 8% of patients with mBC (Grade 4=0.4%) and 22% developed a new or worsening neuropathy that had not recovered within a median follow-up duration of 269 days (range 25-662 days). Neuropathy lasting >1 year occurred in 5% of patients with mBC.

周围神经病变：8%的mBC患者发生3级周围神经病变（4级=0.4%），22%发生新的或恶化的神经病变，在中位随访时间269天（范围25-662天）内未恢复。5%的mBC患者发生持续>1年的神经病变。

Patients should be monitored for signs of peripheral motor and sensory neuropathy. Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral neuropathy until resolution to Grade 2 or less..

应监测患者的周围运动和感觉神经病迹象。在经历3级或4级周围神经病变的患者中保留哈拉文，直到达到2级或更低。。

Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with HALAVEN and for at least 2 weeks following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with HALAVEN and for 3.5 months following the final dose..

胚胎-胎儿毒性：哈拉文给孕妇服用时会对胎儿造成伤害。建议具有生殖潜力的女性在使用哈拉文治疗期间以及在最终剂量后至少2周内使用有效的避孕方法。建议有生殖潜力的女性伴侣的男性在接受哈拉文治疗期间以及最终剂量后3.5个月内使用有效的避孕措施。。

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN and monitor these electrolytes periodically during therapy.

QT间期延长：监测充血性心力衰竭，缓慢性心律失常，已知延长QT间期的药物和电解质异常患者的QT间期延长。在开始哈拉文之前纠正低钾血症或低镁血症，并在治疗期间定期监测这些电解质。

Avoid in patients with congenital long QT syndrome..

避免先天性长QT综合征患者。。

Adverse Reactions

不良反应

In patients with mBC receiving HALAVEN, the most common adverse reactions (≥25%) were neutropenia (82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%), peripheral neuropathy (35%), nausea (35%), and constipation (25%). Febrile neutropenia (4%) and neutropenia (2%) were the most common serious adverse reactions.

在接受哈拉文治疗的mBC患者中，最常见的不良反应（≥25%）是中性粒细胞减少症（82%），贫血（58%），虚弱/疲劳（54%），脱发（45%），周围神经病变（35%），恶心（35%）和便秘（25%）。发热性中性粒细胞减少症（4%）和中性粒细胞减少症（2%）是最常见的严重不良反应。

The most common adverse reaction resulting in discontinuation was peripheral neuropathy (5%)..

导致停药的最常见不良反应是周围神经病变（5%）。。

In patients with liposarcoma and leiomyosarcoma receiving HALAVEN, the most common adverse reactions (≥25%) reported in patients receiving HALAVEN were fatigue (62%), nausea (41%), alopecia (35%), constipation (32%), peripheral neuropathy (29%), abdominal pain (29%), and pyrexia (28%). The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia (32%), hypokalemia (5.4%), and hypocalcemia (5%).

在接受HALAVEN治疗的脂肪肉瘤和平滑肌肉瘤患者中，接受HALAVEN治疗的患者最常见的不良反应（≥25%）是疲劳（62%），恶心（41%），脱发（35%），便秘（32%），周围神经病变（29%），腹痛（29%）和发热（28%）。接受HALAVEN治疗的患者报告的最常见（≥5%）的3-4级实验室异常是中性粒细胞减少症（32%），低钾血症（5.4%）和低钙血症（5%）。

Neutropenia (4.9%) and pyrexia (4.5%) were the most common serious adverse reactions. The most common adverse reactions resulting in discontinuation were fatigue and thrombocytopenia (0.9% each)..

中性粒细胞减少（4.9%）和发热（4.5%）是最常见的严重不良反应。导致停药的最常见不良反应是疲劳和血小板减少（各0.9%）。。

Use in Specific Populations

在特定人群中使用

Lactation: Because of the potential for serious adverse reactions in breastfed infants from eribulin mesylate, advise women not to breastfeed during treatment with HALAVEN and for 2 weeks after the final dose.

哺乳期：由于甲磺酸依立布林母乳喂养的婴儿可能会产生严重的不良反应，因此建议女性在使用哈拉文治疗期间以及服用最终剂量后2周内不要母乳喂养。

Hepatic and Renal Impairment: A reduction in starting dose is recommended for patients with mild or moderate hepatic impairment and/or moderate or severe renal impairment.

肝和肾功能损害：对于轻度或中度肝功能损害和/或中度或重度肾功能损害的患者，建议减少起始剂量。

For more information about HALAVEN, click here for the full Prescribing Information.

有关HALAVEN的更多信息，请单击此处获取完整的处方信息。

HALAVEN® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

HALAVEN®是卫材公司根据卫材研发管理有限公司的许可使用的注册商标。

About LENVIMA® (lenvatinib) Capsules

关于LENVIMA®（lenvatinib）胶囊

LENVIMA is indicated:

LENVIMA表示：

For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)

用于治疗局部复发或转移性，进行性，放射性碘难治性分化型甲状腺癌（DTC）的成年患者

In combination with pembrolizumab, for the first line treatment of adult patients with advanced renal cell carcinoma (RCC)

与pembrolizumab联合用于成人晚期肾细胞癌（RCC）患者的一线治疗

In combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy

联合依维莫司治疗成人晚期肾细胞癌（RCC）患者

For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)

用于不可切除肝细胞癌（HCC）患者的一线治疗

In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation..

与pembrolizumab联合使用，用于治疗晚期子宫内膜癌（EC）患者，该患者通过FDA批准的测试确定为错配修复熟练（pMMR），或者不是微卫星不稳定性高（MSI-H），这些患者在任何情况下都有先前全身治疗后的疾病进展，并且不适合进行根治性手术或放疗。。

LENVIMA, discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFRA), KIT, and RET.

由Eisai发现和开发的LENVIMA是一种多受体酪氨酸激酶抑制剂，可抑制血管内皮生长因子（VEGF）受体VEGFR1（FLT1），VEGFR2（KDR）和VEGFR3（FLT4）的激酶活性。LENVIMA除了正常的细胞功能外，还抑制其他与致病性血管生成，肿瘤生长和癌症进展有关的激酶，包括成纤维细胞生长因子（FGF）受体FGFR1-4，血小板衍生生长因子受体α（PDGFRA），KIT和RET。

Lenvatinib also exhibited antiproliferative activity in hepatocellular carcinoma cell lines dependent on activated FGFR signaling with a concurrent inhibition of FGF-receptor substrate 2 alpha (FRS2) phosphorylation. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone.

Lenvatinib在依赖于活化的FGFR信号传导的肝细胞癌细胞系中也表现出抗增殖活性，同时抑制FGF受体底物2α（FRS2）磷酸化。在同基因小鼠肿瘤模型中，lenvatinib与抗PD-1单克隆抗体的组合减少了肿瘤相关巨噬细胞，增加了活化的细胞毒性T细胞，并且与单独的任一治疗相比表现出更大的抗肿瘤活性。

The combination of LENVIMA and everolimus showed increased antiangiogenic and antitumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone..

LENVIMA和依维莫司的组合显示出增加的抗血管生成和抗肿瘤活性，如体外人内皮细胞增殖，管形成和VEGF信号传导的减少以及人肾细胞癌的小鼠异种移植模型中的肿瘤体积大于单独的每种药物所证明的。。

Important Safety Information for LENVIMA

LENVIMA的重要安全信息

Warnings and Precautions

警告和注意事项

Hypertension. In DTC (differentiated thyroid cancer), hypertension occurred in 73% of patients on LENVIMA (44% grade 3-4). In RCC (renal cell carcinoma), hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% of patients, and 21% had diastolic blood pressure ≥100 mmHg.

高血压。在DTC（分化型甲状腺癌）中，73%的LENVIMA患者发生高血压（44%为3-4级）。在RCC（肾细胞癌）中，42%的LENVIMA+依维莫司患者发生高血压（13%为3级）。29%的患者收缩压≥160 mmHg，21%的患者舒张压≥100 mmHg。

In HCC (hepatocellular carcinoma), hypertension occurred in 45% of LENVIMA-treated patients (24% grade 3). Grade 4 hypertension was not reported in HCC..

在HCC（肝细胞癌）中，45%的LENVIMA治疗患者（24%为3级）发生高血压。HCC中未报告4级高血压。。

Serious complications of poorly controlled hypertension have been reported. Control blood pressure prior to initiation. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at reduced dose when hypertension is controlled or permanently discontinue based on severity..

据报道，高血压控制不佳的严重并发症。在开始之前控制血压。1周后监测血压，然后在前2个月每2周监测一次，然后在治疗期间至少每月监测一次。当高血压得到控制或根据严重程度永久停止时，停止并以减少的剂量恢复。。

Cardiac Dysfunction. Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC, and HCC, grade 3 or higher cardiac dysfunction occurred in 3% of LENVIMA-treated patients. Monitor for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

心脏功能障碍。LENVIMA可能会发生严重致命的心脏功能障碍。在799例DTC，RCC和HCC患者的临床试验中，3%的LENVIMA治疗患者发生3级或更高级别的心脏功能障碍。监测心脏功能障碍的临床症状或体征。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Arterial Thromboembolic Events. Among patients receiving LENVIMA or LENVIMA + everolimus, arterial thromboembolic events of any severity occurred in 2% of patients in RCC and HCC and 5% in DTC. Grade 3-5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials.

动脉血栓栓塞事件。在接受LENVIMA或LENVIMA+依维莫司治疗的患者中，2%的RCC和HCC患者发生任何严重程度的动脉血栓栓塞事件，5%的DTC患者发生动脉血栓栓塞事件。在所有临床试验中，3-5级动脉血栓栓塞事件的发生率为2%至3%。

Among patients receiving LENVIMA with pembrolizumab, arterial thrombotic events of any severity occurred in 5% of patients in CLEAR, including myocardial infarction (3.4%) and cerebrovascular accident (2.3%).

在接受LENVIMA联合pembrolizumab治疗的患者中，5%的CLEAR患者发生任何严重程度的动脉血栓形成事件，包括心肌梗死（3.4%）和脑血管意外（2.3%）。

Permanently discontinue following an arterial thrombotic event. The safety of resuming after an arterial thromboembolic event has not been established, and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

动脉血栓形成事件后永久停药。动脉血栓栓塞事件后恢复的安全性尚未确定，LENVIMA尚未在过去6个月内发生动脉血栓栓塞事件的患者中进行研究。

Hepatotoxicity. Across clinical studies enrolling 1327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events, including hepatic failure, acute hepatitis, and hepatorenal syndrome, occurred in 0.5% of patients. In HCC, hepatic encephalopathy occurred in 8% of LENVIMA-treated patients (5% grade 3-5).

肝毒性。在招募1327名LENVIMA治疗的HCC以外的恶性肿瘤患者的临床研究中，1.4%的患者发生了严重的肝脏不良反应。0.5%的患者发生致命事件，包括肝衰竭，急性肝炎和肝肾综合征。在HCC中，8%的LENVIMA治疗患者发生肝性脑病（5%为3-5级）。

Grade 3-5 hepatic failure occurred in 3% of LENVIMA-treated patients; 2% of patients discontinued LENVIMA due to hepatic encephalopathy, and 1% discontinued due to hepatic failure..

3%的LENVIMA治疗患者发生3-5级肝衰竭；2%的患者因肝性脑病停用LENVIMA，1%因肝衰竭停用。。

Monitor liver function prior to initiation, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

在开始之前监测肝功能，然后在前2个月每2周监测一次，然后在治疗期间至少每月监测一次。密切监测HCC患者的肝衰竭迹象，包括肝性脑病。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Renal Failure or Impairment. Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment was reported in 14% and 7% of LENVIMA-treated patients in DTC and HCC, respectively. Grade 3-5 renal failure or impairment occurred in 3% of patients with DTC and 2% of patients with HCC, including 1 fatal event in each study.

肾功能衰竭或损害。LENVIMA可能会发生严重的，包括致命的肾衰竭或损害。在DTC和HCC中，LENVIMA治疗的患者中分别有14%和7%报告了肾功能损害。3%的DTC患者和2%的HCC患者发生3-5级肾功能衰竭或损害，每项研究中包括1例致命事件。

In RCC, renal impairment or renal failure was reported in 18% of LENVIMA + everolimus–treated patients (10% grade 3)..

在肾细胞癌中，18%的LENVIMA+依维莫司治疗患者（10%为3级）报告肾功能不全或肾衰竭。。

Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at reduced dose upon recovery or permanently discontinue for renal failure or impairment based on severity.

立即处理腹泻或脱水/血容量不足。恢复后停止并以减少的剂量恢复，或根据严重程度因肾衰竭或损害而永久停药。

Proteinuria. In DTC and HCC, proteinuria was reported in 34% and 26% of LENVIMA-treated patients, respectively. Grade 3 proteinuria occurred in 11% and 6% in DTC and HCC, respectively. In RCC, proteinuria occurred in 31% of patients receiving LENVIMA + everolimus (8% grade 3). Monitor for proteinuria prior to initiation and periodically during treatment.

蛋白尿。在DTC和HCC中，分别有34%和26%的LENVIMA治疗患者报告有蛋白尿。DTC和HCC的3级蛋白尿发生率分别为11%和6%。在RCC中，接受LENVIMA+依维莫司治疗的患者中有31%发生蛋白尿（3级8%）。开始前和治疗期间定期监测蛋白尿。

If urine dipstick proteinuria ≥2+ is detected, obtain a 24-hour urine protein. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

如果检测到尿试纸蛋白尿≥2+，则获得24小时尿蛋白。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Diarrhea. Of the 737 LENVIMA-treated patients in DTC and HCC, diarrhea occurred in 49% (6% grade 3). In RCC, diarrhea occurred in 81% of LENVIMA + everolimus–treated patients (19% grade 3). Diarrhea was the most frequent cause of dose interruption/reduction, and diarrhea recurred despite dose reduction.

腹泻。在737例LENVIMA治疗的DTC和HCC患者中，腹泻发生率为49%（6%为3级）。在RCC中，81%的LENVIMA+依维莫司治疗患者发生腹泻（19%为3级）。腹泻是剂量中断/减少的最常见原因，尽管剂量减少，腹泻仍会复发。

Promptly initiate management of diarrhea. Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity..

及时启动腹泻管理。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。。

Fistula Formation and Gastrointestinal Perforation. Of the 799 patients treated with LENVIMA or LENVIMA + everolimus in DTC, RCC, and HCC, fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue in patients who develop gastrointestinal perforation of any severity or grade 3-4 fistula..

瘘管形成和胃肠穿孔。在DTC，RCC和HCC中用LENVIMA或LENVIMA+依维莫司治疗的799例患者中，瘘管或胃肠道穿孔发生率为2%。发生任何严重程度的胃肠道穿孔或3-4级瘘管的患者永久停药。。

QT Interval Prolongation. In DTC, QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%. In RCC, QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA + everolimus and QTc interval >500 ms occurred in 6%.

QT间隔延长。在DTC中，9%的LENVIMA治疗患者发生QT/QTc间期延长，2%的患者发生QT间期延长>500 ms。在RCC中，接受LENVIMA+依维莫司治疗的患者中有11%的QTc间隔增加>60 ms，而QTc间隔>500 ms的患者发生率为6%。

In HCC, QTc interval increases of >60 ms occurred in 8% of LENVIMA-treated patients and QTc interval >500 ms occurred in 2%..

在HCC中，8%的LENVIMA治疗患者的QTc间隔增加>60 ms，2%的患者QTc间隔>500 ms。。

Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics.

在基线和治疗期间定期监测和纠正电解质异常。监测先天性长QT综合征、充血性心力衰竭、缓慢性心律失常患者或服用已知延长QT间期药物（包括Ia类和III类抗心律失常药物）的患者的心电图。

Withhold and resume at reduced dose upon recovery based on severity..

根据严重程度恢复后，以减少的剂量停止并恢复。。

Hypocalcemia. In DTC, grade 3-4 hypocalcemia occurred in 9% of LENVIMA-treated patients. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation with or without dose interruption or dose reduction. In RCC, grade 3-4 hypocalcemia occurred in 6% of LENVIMA + everolimus–treated patients.

低钙血症。在DTC中，9%的LENVIMA治疗患者发生3-4级低钙血症。在65%的病例中，低钙血症在补充钙后得到改善或解决，无论是否有剂量中断或剂量减少。在RCC中，LENVIMA+依维莫司治疗的患者中有6%发生3-4级低钙血症。

In HCC, grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients. Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity..

在HCC中，0.8%的LENVIMA治疗患者发生3级低钙血症。至少每月监测血钙水平，并在治疗期间根据需要更换钙。恢复后停止并以减少的剂量恢复，或根据严重程度永久停止。。

Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Across clinical studies of 1823 patients who received LENVIMA as a single agent, RPLS occurred in 0.3%. Confirm diagnosis of RPLS with MRI. Withhold and resume at reduced dose upon recovery or permanently discontinue depending on severity and persistence of neurologic symptoms..

可逆性后部白质脑病综合征（RPLS）。在1823名接受LENVIMA作为单一药物的患者的临床研究中，RPL发生率为0.3%。通过MRI确认RPLS的诊断。根据神经系统症状的严重程度和持续性，停止并在恢复后以减少的剂量恢复或永久停止。。

Hemorrhagic Events. Serious including fatal hemorrhagic events can occur with LENVIMA. In DTC, RCC, and HCC clinical trials, hemorrhagic events, of any grade, occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria.

出血事件。LENVIMA可能发生严重的出血事件，包括致命的出血事件。在DTC，RCC和HCC临床试验中，799例使用LENVIMA作为单一药物或与依维莫司联合治疗的患者中，有29%发生了任何级别的出血事件。最常报告的出血事件（所有级别，至少5%的患者发生）是鼻出血和血尿。

In DTC, grade 3-5 hemorrhage occurred in 2% of LENVIMA-treated patients, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In RCC, grade 3-5 hemorrhage occurred in 8% of LENVIMA + everolimus–treated patients, including 1 fatal cerebral hemorrhage.

在DTC中，2%的LENVIMA治疗患者发生3-5级出血，其中16例接受LENVIMA治疗并在基线时发生中枢神经系统转移的患者中有1例致命性颅内出血。在RCC中，LENVIMA+依维莫司治疗的患者中有8%发生3-5级出血，其中包括1例致命性脑出血。

In HCC, grade 3-5 hemorrhage occurred in 5% of LENVIMA-treated patients, including 7 fatal hemorrhagic events. Serious tumor-related bleeds, including fatal hemorrhagic events, occurred in LENVIMA-treated patients in clinical trials and in the postmarketing setting. In postmarketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than other tumors.

在HCC中，5%的LENVIMA治疗患者发生3-5级出血，包括7例致命的出血事件。在临床试验和上市后环境中，LENVIMA治疗的患者发生了严重的肿瘤相关出血，包括致命的出血事件。在上市后监测中，甲状腺未分化癌（ATC）患者比其他肿瘤更容易出现严重致命的颈动脉出血。

Safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials..

LENVIMA在ATC患者中的安全性和有效性尚未在临床试验中得到证实。。

Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (eg, carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue based on severity.

考虑与肿瘤侵袭或主要血管（例如颈动脉）浸润相关的严重或致命出血的风险。恢复后以减少的剂量停止并恢复，或根据严重程度永久停止。

Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction. LENVIMA impairs exogenous thyroid suppression. In DTC, 88% of patients had baseline thyroid stimulating hormone (TSH) level ≤0.5 mU/L. In patients with normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients.

促甲状腺激素抑制/甲状腺功能障碍受损。LENVIMA损害外源性甲状腺抑制。在DTC中，88%的患者基线促甲状腺激素（TSH）水平≤0.5 mU/L。在基线TSH正常的患者中，57%的LENVIMA治疗患者的TSH水平在基线后升高>0.5 mU/L。

In RCC and HCC, grade 1 or 2 hypothyroidism occurred in 24% of LENVIMA + everolimus–treated patients and 21% of LENVIMA-treated patients, respectively. In patients with normal or low TSH at baseline, elevation of TSH was observed post baseline in 70% of LENVIMA-treated patients in HCC and 60% of LENVIMA + everolimus–treated patients in RCC..

在RCC和HCC中，分别有24%的LENVIMA+依维莫司治疗患者和21%的LENVIMA治疗患者发生1级或2级甲状腺功能减退症。在基线TSH正常或低的患者中，70%的LENVIMA治疗的HCC患者和60%的LENVIMA+依维莫司治疗的RCC患者在基线后观察到TSH升高。。

Monitor thyroid function prior to initiation and at least monthly during treatment. Treat hypothyroidism according to standard medical practice.

在开始之前和治疗期间至少每月监测甲状腺功能。根据标准医疗实践治疗甲状腺功能减退症。

Impaired Wound Healing. Impaired wound healing has been reported in patients who received LENVIMA. Withhold LENVIMA for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of LENVIMA after resolution of wound healing complications has not been established..

伤口愈合受损。据报道，接受LENVIMA治疗的患者伤口愈合受损。在选择性手术前至少1周保留LENVIMA。大手术后至少2周内不要给药，直到伤口充分愈合。伤口愈合并发症解决后恢复LENVIMA的安全性尚未确定。。

Osteonecrosis of the Jaw (ONJ). ONJ has been reported in patients receiving LENVIMA. Concomitant exposure to other risk factors, such as bisphosphonates, denosumab, dental disease, or invasive dental procedures, may increase the risk of ONJ.

颌骨坏死（ONJ）。据报道，接受LENVIMA的患者患有ONJ。同时暴露于其他风险因素，如双膦酸盐，denosumab，牙科疾病或侵入性牙科手术，可能会增加ONJ的风险。

Perform an oral examination prior to treatment with LENVIMA and periodically during LENVIMA treatment. Advise patients regarding good oral hygiene practices and to consider having preventive dentistry performed prior to treatment with LENVIMA and throughout treatment with LENVIMA.Avoid invasive dental procedures, if possible, while on LENVIMA treatment, particularly in patients at higher risk.

在使用LENVIMA治疗之前和LENVIMA治疗期间定期进行口腔检查。建议患者注意良好的口腔卫生习惯，并考虑在使用LENVIMA治疗之前和整个使用LENVIMA治疗期间进行预防性牙科治疗。如果可能的话，在使用LENVIMA治疗时，避免进行侵入性牙科手术，特别是在风险较高的患者中。

Withhold LENVIMA for at least 1 week prior to scheduled dental surgery or invasive dental procedures, if possible. For patients requiring invasive dental procedures, discontinuation of bisphosphonate treatment may reduce the risk of ONJ.Withhold LENVIMA if ONJ develops and restart based on clinical judgement of adequate resolution.Embryo-Fetal Toxicity.

如果可能的话，在预定的牙科手术或侵入性牙科手术之前，扣留LENVIMA至少1周。对于需要侵入性牙科手术的患者，停止双膦酸盐治疗可能会降低ONJ的风险。如果ONJ发展并根据足够分辨率的临床判断重新启动，则扣留LENVIMA。胚胎-胎儿毒性。

Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to pregnant women. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended clinical doses resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits.

根据其作用机制和动物繁殖研究的数据，LENVIMA在给孕妇服用时会造成胎儿伤害。在动物繁殖研究中，在器官发生过程中以低于推荐临床剂量的剂量口服lenvatinib会导致大鼠和兔子的胚胎毒性，胎儿毒性和致畸性。

Advise pregnant women of the potential risk to a fetus and advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for 30 days after the last dose..

建议孕妇注意胎儿的潜在风险，并建议有生殖潜力的女性在服用LENVIMA期间和最后一剂后30天内使用有效的避孕措施。。

Adverse ReactionsIn DTC, the most common adverse reactions (≥30%) observed in LENVIMA-treated patients were hypertension (73%), fatigue (67%), diarrhea (67%), arthralgia/myalgia (62%), decreased appetite (54%), decreased weight (51%), nausea (47%), stomatitis (41%), headache (38%), vomiting (36%), proteinuria (34%), palmar-plantar erythrodysesthesia syndrome (32%), abdominal pain (31%), and dysphonia (31%).

不良反应在DTC中，LENVIMA治疗患者最常见的不良反应（≥30%）是高血压（73%），疲劳（67%），腹泻（67%），关节痛/肌痛（62%），食欲下降（54%），体重下降（51%），恶心（47%），口腔炎（41%），头痛（38%），呕吐（36%），蛋白尿（34%），掌底红细胞感觉异常综合征（32%），腹痛（31%）和发音困难（31%）。

The most common serious adverse reactions (≥2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of LENVIMA-treated patients; 18% discontinued LENVIMA. The most common adverse reactions (≥10%) resulting in dose reductions were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%)..

最常见的严重不良反应（≥2%）是肺炎（4%），高血压（3%）和脱水（3%）。不良反应导致68%的LENVIMA治疗患者的剂量减少；18%停止服用LENVIMA。导致剂量减少的最常见不良反应（≥10%）是高血压（13%），蛋白尿（11%），食欲下降（10%）和腹泻（10%）；导致停用LENVIMA的最常见不良反应（≥1%）是高血压（1%）和虚弱（1%）。。

In RCC, the most common adverse reactions (≥20%) observed in LENVIMA + pembrolizumab-treated patients were fatigue (63%), diarrhea (62%), musculoskeletal pain (58%), hypothyroidism (57%), hypertension (56%), stomatitis (43%), decreased appetite (41%), rash (37%), nausea (36%), decreased weight (30%), dysphonia (30%), proteinuria (30%), palmar-plantar erythrodysesthesia syndrome (29%), abdominal pain (27%), hemorrhagic events (27%), vomiting (26%), constipation (25%), hepatotoxicity (25%), headache (23%), and acute kidney injury (21%).

在RCC中，在LENVIMA+pembrolizumab治疗的患者中观察到的最常见的不良反应（≥20%）是疲劳（63%），腹泻（62%），肌肉骨骼疼痛（58%），甲状腺功能减退（57%），高血压（56%），口腔炎（43%），食欲下降（41%），皮疹（37%），恶心（36%），体重减轻（30%），发音困难（30%），蛋白尿（30%），掌底红细胞感觉异常综合征（29%），腹痛（27%），出血事件（27%），呕吐（26%），便秘（25%），肝毒性（25%），头痛（23%）和急性肾损伤（21%）。

The most common serious adverse reactions (≥2%) were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%). Fatal adverse reactions occurred in 4.3% of patients receiving LENVIMA in combination with pembrolizumab, including cardio-respiratory arrest (0.9%), sepsis (0.9%), and one case (0.3%) each of arrhythmia, autoimmune hepatitis, dyspnea, hypertensive crisis, increased blood creatinine, multiple organ dysfunction syndrome, myasthenic syndrome, myocarditis, nephritis, pneumonitis, ruptured aneurysm and subarachnoid hemorrhage.

最常见的严重不良反应（≥2%）是出血事件（5%），腹泻（4%），高血压（3%），心肌梗塞（3%），肺炎（3%），呕吐（3%），急性肾损伤（2%），肾上腺功能不全（2%），呼吸困难（2%）和肺炎（2%）。4.3%接受LENVIMA联合pembrolizumab治疗的患者发生致命不良反应，包括心肺骤停（0.9%），败血症（0.9%），心律失常，自身免疫性肝炎，呼吸困难，高血压危象，血肌酐升高，多器官功能障碍综合征，肌无力综合征，心肌炎，肾炎，肺炎，动脉瘤破裂和蛛网膜下腔出血各1例（0.3%）。

Serious adverse reactions occurred in 51% of patients receiving LENVIMA and pembrolizumab. Serious adverse reactions in ≥2% of patients were hemorrhagic events (5%), diarrhea (4%), hypertension (3%), myocardial infarction (3%), pneumonitis (3%), vomiting (3%), acute kidney injury (2%), adrenal insufficiency (2%), dyspnea (2%), and pneumonia (2%).

51%接受LENVIMA和pembrolizumab治疗的患者发生严重不良反应。≥2%的患者严重不良反应为出血事件（5%），腹泻（4%），高血压（3%），心肌梗死（3%），肺炎（3%），呕吐（3%），急性肾损伤（2%），肾上腺功能不全（2%），呼吸困难（2%）和肺炎（2%）。

Permanent discontinuation of LENVIMA, pembrolizumab, or both due to an adverse reaction occurred in 37% of patients; 26% LENVIMA only, 29% pembrolizumab only, and 13% both drugs. The most common adverse reactions (≥2%) lea.

37%的患者因不良反应而永久停用LENVIMA，pembrolizumab或两者；仅26%的LENVIMA，仅29%的pembrolizumab，以及13%的两种药物。最常见的不良反应（≥2%）lea。

In RCC, the most common adverse reactions (≥30%) observed in LENVIMA + everolimus–treated patients were diarrhea (81%), fatigue (73%), arthralgia/myalgia (55%), decreased appetite (53%), vomiting (48%), nausea (45%), stomatitis (44%), hypertension (42%), peripheral edema (42%), cough (37%), abdominal pain (37%), dyspnea (35%), rash (35%), decreased weight (34%), hemorrhagic events (32%), and proteinuria (31%).

在RCC中，LENVIMA+依维莫司治疗的患者最常见的不良反应（≥30%）是腹泻（81%），疲劳（73%），关节痛/肌痛（55%），食欲下降（53%），呕吐（48%），恶心（45%），口腔炎（44%），高血压（42%），外周水肿（42%），咳嗽（37%），腹痛（37%），呼吸困难（35%），皮疹（35%），体重减轻（34%），出血事件（32%）和蛋白尿（31%）。

The most common serious adverse reactions (≥5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%).

最常见的严重不良反应（≥5%）是肾功能衰竭（11%），脱水（10%），贫血（6%），血小板减少症（5%），腹泻（5%），呕吐（5%）和呼吸困难（5%）。不良反应导致89%的患者剂量减少或中断。导致剂量减少的最常见不良反应（≥5%）是腹泻（21%），疲劳（8%），血小板减少症（6%），呕吐（6%），恶心（5%）和蛋白尿（5%）。

Treatment discontinuation due to an adverse reaction occurred in 29% of patients..

29%的患者因不良反应而停止治疗。。

In HCC, the most common adverse reactions (≥20%) observed in LENVIMA-treated patients were hypertension (45%), fatigue (44%), diarrhea (39%), decreased appetite (34%), arthralgia/myalgia (31%), decreased weight (31%), abdominal pain (30%), palmar-plantar erythrodysesthesia syndrome (27%), proteinuria (26%), dysphonia (24%), hemorrhagic events (23%), hypothyroidism (21%), and nausea (20%).

在HCC中，在LENVIMA治疗的患者中观察到的最常见的不良反应（≥20%）是高血压（45%），疲劳（44%），腹泻（39%），食欲下降（34%），关节痛/肌痛（31%），体重下降（31%），腹痛（30%），掌底红细胞感觉障碍综合征（27%），蛋白尿（26%），发音困难（24%），出血事件（23%），甲状腺功能减退症（21%）和恶心（20%）。

The most common serious adverse reactions (≥2%) were hepatic encephalopathy (5%), hepatic failure (3%), ascites (3%), and decreased appetite (2%). Adverse reactions led to dose reductions or interruption in 62% of patients. The most common adverse reactions (≥5%) resulting in dose reductions were fatigue (9%), decreased appetite (8%), diarrhea (8%), proteinuria (7%), hypertension (6%), and palmar-plantar erythrodysesthesia syndrome (5%).

最常见的严重不良反应（≥2%）是肝性脑病（5%），肝衰竭（3%），腹水（3%）和食欲下降（2%）。不良反应导致62%的患者剂量减少或中断。导致剂量减少的最常见不良反应（≥5%）是疲劳（9%），食欲下降（8%），腹泻（8%），蛋白尿（7%），高血压（6%）和掌底红细胞感觉异常综合征（5%）。

Treatment discontinuation due to an adverse reaction occurred in 20% of patients. The most common adverse reactions (≥1%) resulting in discontinuation of LENVIMA were fatigue (1%), hepatic encephalopathy (2%), hyperbilirubinemia (1%), and hepatic failure (1%)..

20%的患者因不良反应而停止治疗。导致停用LENVIMA的最常见不良反应（≥1%）是疲劳（1%），肝性脑病（2%），高胆红素血症（1%）和肝衰竭（1%）。。

In EC, the most common adverse reactions (≥20%) observed in LENVIMA and pembrolizumab–treated patients were hypothyroidism (67%), hypertension (67%), fatigue (58%), diarrhea (55%), musculoskeletal disorders (53%), nausea (49%), decreased appetite (44%), vomiting (37%), stomatitis (35%), decreased weight (34%), abdominal pain (34%), urinary tract infection (31%), proteinuria (29%), constipation (27%), headache (26%), hemorrhagic events (25%), palmar‐plantar erythrodysesthesia (23%), dysphonia (22%), and rash (20%).

在EC中，在LENVIMA和pembrolizumab治疗的患者中观察到的最常见的不良反应（≥20%）是甲状腺功能减退症（67%），高血压（67%），疲劳（58%），腹泻（55%），肌肉骨骼疾病（53%），恶心（49%），食欲下降（44%），呕吐（37%），口腔炎（35%），体重减轻（34%），腹痛（34%），尿路感染（31%），蛋白尿（29%），便秘（27%），头痛（26%），出血事件（25%），掌底红细胞感觉异常（23%），发音困难（22%）和皮疹（20%）。

Fatal adverse reactions occurred in 4.7% of those treated with LENVIMA and pembrolizumab, including 2 cases of pneumonia, and 1 case of the following: acute kidney injury, acute myocardial infarction, colitis, decreased appetite, intestinal perforation, lower gastrointestinal hemorrhage, malignant gastrointestinal obstruction, multiple organ dysfunction syndrome, myelodysplastic syndrome, pulmonary embolism, and right ventricular dysfunction.

LENVIMA和pembrolizumab治疗组中有4.7%发生致命不良反应，包括2例肺炎，1例以下：急性肾损伤，急性心肌梗死，结肠炎，食欲下降，肠穿孔，下消化道出血，恶性胃肠道梗阻，多器官功能障碍综合征，骨髓增生异常综合征，肺栓塞和右心室功能障碍。

Serious adverse reactions occurred in 50% of patients receiving LENVIMA and pembrolizumab. Serious adverse reactions with frequency ≥3% were hypertension (4.4%), and urinary tract infection (3.2%). Discontinuation of LENVIMA due to an adverse reaction occurred in 26% of patients. The most common (≥1%) adverse reactions leading to discontinuation of LENVIMA were hypertension (2%), asthenia (1.8%), diarrhea (1.2%), decreased appetite (1.2%), proteinuria (1.2%), and vomiting (1.2%).

接受LENVIMA和pembrolizumab治疗的患者中有50%发生严重不良反应。频率≥3%的严重不良反应为高血压（4.4%）和尿路感染（3.2%）。26%的患者因不良反应而停止服用LENVIMA。导致停用LENVIMA的最常见（≥1%）不良反应是高血压（2%），虚弱（1.8%），腹泻（1.2%），食欲下降（1.2%），蛋白尿（1.2%）和呕吐（1.2%）。

Dose reductions of LENVIMA due to adverse reactions occurred in 67% of patients. The most common (≥5%) adverse reactions resulting in dose reduction of LENVIMA were hypertension (18%), diarrhea (11%), palmar-plantar erythrodysesthesia syndrome (9%), proteinuria (7%), fatigue (7%), decreased appetite (6%), asthenia (5%), and weight decreased (5%)..

67%的患者因不良反应而减少了LENVIMA的剂量。导致LENVIMA剂量减少的最常见（≥5%）不良反应是高血压（18%），腹泻（11%），掌底红细胞感觉异常综合征（9%），蛋白尿（7%），疲劳（7%），食欲下降（6%），虚弱（5%）和体重下降（5%）。。

Use in Specific PopulationsBecause of the potential for serious adverse reactions in breastfed children, advise women to discontinue breastfeeding during treatment and for 1 week after the last dose. LENVIMA may impair fertility in males and females of reproductive potential.

在特定人群中使用由于母乳喂养儿童可能产生严重不良反应，建议女性在治疗期间和最后一次服用后1周停止母乳喂养。LENVIMA可能会损害具有生殖潜力的男性和女性的生育能力。

No dose adjustment is recommended for patients with mild (CLcr 60-89 mL/min) or moderate (CLcr 30-59 mL/min) renal impairment. LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe (CLcr 15-29 mL/min) renal impairment. Reduce the dose for patients with DTC, RCC, or EC and severe renal impairment.

对于轻度（CLcr 60-89 mL/min）或中度（CLcr 30-59 mL/min）肾功能不全的患者，不建议进行剂量调整。DTC，RCC或EC和严重（CLcr 15-29 mL/min）肾功能不全患者的LENVIMA浓度可能会增加。减少DTC，RCC或EC和严重肾功能不全患者的剂量。

There is no recommended dose for patients with HCC and severe renal impairment. LENVIMA has not been studied in patients with end-stage renal disease..

HCC和严重肾功能不全患者没有推荐剂量。LENVIMA尚未在终末期肾病患者中进行研究。。

No dose adjustment is recommended for patients with HCC and mild hepatic impairment (Child-Pugh A). There is no recommended dose for patients with HCC with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. No dose adjustment is recommended for patients with DTC, RCC, or EC and mild or moderate hepatic impairment.

对于HCC和轻度肝损伤（Child-Pugh A）患者，不建议调整剂量。对于中度（Child-Pugh B）或重度（Child-Pugh C）肝功能损害的HCC患者，没有推荐剂量。对于DTC，RCC或EC以及轻度或中度肝功能损害的患者，不建议调整剂量。

LENVIMA concentrations may increase in patients with DTC, RCC, or EC and severe hepatic impairment. Reduce the dose for patients with DTC, RCC, or EC and severe hepatic impairment..

DTC，RCC或EC和严重肝损伤患者的LENVIMA浓度可能会增加。减少DTC，RCC或EC和严重肝损伤患者的剂量。。

LENVIMA (lenvatinib) is available as 10 mg and 4 mg capsules.

乐伐替尼有10 mg和4 mg两种胶囊。

Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf

请参阅LENVIMA（lenvatinib）的处方信息http://www.lenvima.com/pdfs/prescribing-information.pdf

About the Eisai and Merck Strategic CollaborationIn March 2018, Eisai and Merck, known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with Merck's anti-PD-1 therapy KEYTRUDA.

关于卫材和默克的战略合作2018年3月，卫材和默克（在美国和加拿大以外称为MSD）通过一家附属公司，就LENVIMA的全球共同开发和共同商业化达成了战略合作。根据该协议，两家公司共同开发、制造和商业化LENVIMA，既可以作为单一疗法，也可以与默克公司的抗PD-1疗法KEYTRUDA联合使用。

Eisai and Merck are studying the KEYTRUDA plus LENVIMA combination through the LEAP (LEnvatinib And Pembrolizumab) clinical program in various tumor types across multiple clinical trials..

Eisai和Merck正在通过LEAP（LEnvatinib和Pembrolizumab）临床计划研究KEYTRUDA加LENVIMA组合在多种临床试验中的各种肿瘤类型。。

About EisaiEisai's Corporate Concept is 'to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides.' Under this Concept [also known as our human health care (hhc) Concept], we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities.

关于卫材卫材的企业理念是“首先考虑患者和日常生活领域的人们，并增加医疗保健提供的益处。”根据这一概念[也称为我们的人类卫生保健（hhc）概念]，我们的目标是以缓解对健康的焦虑和减少健康差距的形式有效实现社会福利。

With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology..

凭借由研发设施、生产基地和营销子公司组成的全球网络，我们致力于创造和交付创新产品，以针对医疗需求高度未满足的疾病，特别关注我们的神经病学和肿瘤学战略领域。。

In addition, our continued commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), is demonstrated by our work on various activities together with global partners.

此外，我们继续致力于消除被忽视的热带病（NTDs），这是联合国可持续发展目标（SDGs）的一个目标（3.3），我们与全球合作伙伴一起开展的各种活动证明了这一点。

For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), us.eisai.com (for U.S. headquarters: Eisai Inc.) or www.eisai.eu (for Europe, Middle East, Africa, Russia, Australia, and New Zealand headquarters: Eisai Europe Ltd.), and connect with us on Twitter (U.S. and global) and LinkedIn (for U.S. and EMEA)..

有关Eisai的更多信息，请访问www.Eisai.com（全球总部：Eisai Co.，Ltd.）、美国Eisai.com（美国总部：Eisai Inc.）或www.Eisai.eu（欧洲、中东、非洲、俄罗斯、澳大利亚和新西兰总部：Eisai Europe Ltd.），并通过推特（美国和全球）和LinkedIn（美国和EMEA）与我们联系。。

LENVIMA® is a registered trademark used by Eisai Inc. under license from Eisai R&D Management Co., Ltd.

LENVIMA®是Eisai Inc.根据Eisai研发管理有限公司的许可使用的注册商标。

©2024 Eisai Inc. All Rights Reserved.

©2024 Eisai Inc.保留所有权利。

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, N.J., U.S.A.

KEYTRUDA® 是美国新泽西州拉威市默克公司股份有限公司子公司默克夏普多姆有限责任公司的注册商标。

SOURCE Eisai Inc.

SOURCE Eisai公司。